Hyperbilirubinemia and pigment
gallstones are frequent complications in transfusion-dependent β-
thalassemia (TDβT) patients.
Bilirubin production and clearance are determined by genetic as well as environmental variables like ineffective erythropoiesis,
hemolysis,
infection-induced hepatic injury, and
drug- or
iron-related toxicities. We studied the frequency of the
Gilbert syndrome (GS), a common hereditary cause of
hyperbilirubinemia in 102 TDβT patients aged 13-43 years (median 26 years). Total and unconjugated
hyperbilirubinemia were frequent (81.4% and 84.3% patients respectively). Twenty (19.6%) patients showed total
bilirubin > 3.0 mg/dL; 53 (51.9%) had an elevation of either
alanine or
aspartate aminotransferase, or
alkaline phosphatase liver
enzymes. Nineteen (18.6% of the 92 tested) were positive for
hepatitis B or C, or HIV. The mean total and unconjugated
bilirubin levels and AST, ALT, and ALP levels in patients positive for
hepatitis B or C were not significantly different from negative cases. Eighteen patients (17.7%) had GS: homozygous (TA)7/7 UGT1A1 promoter motif (the *28/*28 genotype), 48 (47.1%) were heterozygous (TA)6/7. Total + unconjugated
bilirubin rose significantly with the (TA)7 allele dose. Fourteen (13.7%) patients had
gallstones. There was no significant difference in total/unconjugated
bilirubin in patients with/without
gallstones and no significant differences in frequencies of
gallstones within the three UGT1A1 genotypes. This largest study in Indian TDβT patients suggests that GS should be excluded in TDβT cases where
jaundice remains unexplained after treatable causes like
infections,
chelator toxicity, or transfusion-related
hemolysis are excluded. GS was not associated with
gallstones, possibly due to a lower incidence of
cholelithiasis overall, a younger age cohort, or other environmental factors.